This project intends to develop a better understanding of the etiology of uninhibited bladder contractions which develop following bladder outlet obstruction. This poorly understood process of bladder outlet obstruction secondary to benign prostatic hyperplasia is responsible for voiding dysfunction in the majority of elderly men and leads 1/3 of all men to eventually undergo prostatic surgery. This study will investigate the influence of prostatic sensory nerve stimulation in the development and maintenance of uninhibited detrusor contractions using male dogs with chronically obstructed bladder outlets. The role of prostate sensory nerves will be examined by surgical denervation of the prostate and prostatic urethra. Five experimental groups will be utilized: Group I--bladder outlet obstruction, Group II--bladder outlet obstruction and prostatic denervation, Group III--prostatic denervation, Group IV--sham operation and Group V--Control. In vivo and in vitro approaches will be utilized. Bladder urodynamic studies will document the presence of obstruction and the development of uninhibited contractions using cystometography, uroflowmetry and bladder pressure flow studies in the awake animal. Subsequent in vitro smooth muscle bath studies of bladder dome and neck isolated from these animals will examine tachykinins as potential sensory nerve transmitters in this system. Immunohistochemical analysis of bladder and prostate tissue will be used to investigate the presence of peptides. Using the same model adrenergic and muscarinic agonist participation will be documented. In addition, the smooth muscle content of adrenergic and muscarinic receptors will be determined and morphologic analysis of the bladder wall using microscopy will document the effects of obstruction and sensory denervation of the prostate. Final statistical analysis will correlate the duration and severity of obstruction and the presence of uninhibited detrusor contractions to the in vivo and in vitro observations. The long-term objectives are to delineate the contribution of sensory neurotransmitters and sensory impulses from the prostate in uninhibited bladder contractions in obstructed bladders. This information will be of significant value in medical treatment of uninhibited bladder contractions.